The central aim of this project is to develop clinical means of assuring infection- and complication-free healing of both chronic and acute wounds. We have made substantial progress toward that goal. As a matter of both theory and clinical practice, perfusion and oxygenation are the most important requirements for repair. We have previously shown that: 1) infection is inversely proportional and collagen is directly proportional to wound tissue oxygen, 2) wound hypoxia is common in both acute and chronic wounds, and 3) wound hypoxia can be prevented or corrected by a number of simple means, including warming, volume replacement, and sympathetic blockade. We now propose to refine and exploit simple, clinically useful means of determining wound perfusion and oxygenation that will allow us: 1) to delineate the ideal conditions for wound healing and how to achieve them; 2) to demonstrate that prognostic indicators of poor healing can be devised that identify potentially useful interventions to improve wound blood flow and oxygenation; and 3) to measure and meet the individual patient's need for wound perfusion and oxygenation to assure healing. In the past we have focused largely on the need to overcome or prevent wound hypoxia, i.e. to create normoxic wounds. Because we have learned to overcome wound hypoxia in many cases we can now develop further evidence regarding the beneficial effects of hyperoxia in control of bacterial injection and in angiogenesis in wounds. Furthermore, we can evaluate cycled hyperoxia (of which hyperbaric oxygen is a subset) as a stimulant to angiogenesis. The proposals in this project rest heavily on Projects 1, 2, and 3. In this regard, the aim of Project 4 is to translate the proposals and previous findings of the basic science projects of this Program from the bench to the bedside.